Neuropathic pain is a chronic pain that results from nerve damage, is characterized by an abnormal hypersensitivity to innocuous as well as noxious stimuli, and often persists after the tissue damage and inflammation that initially caused the pain have healed. Eleven million patients worldwide are afflicted by neuropathic pain (Olsen, WWMR, Inc. Consulting and Marketing Report (2002)). Clinically, neuropathic pain is difficult to manage, fails to respond to standard analgesic treatments, and often worsens over time (Amer et al., Acta Anaesthesiol. Scand. 29:32 (1985); Cherny et al., Neurology 44:857 (1994)).
Spicamycin is an anti-tumor antibiotic produced by the bacterium Streptomyces alansinicus 879-MT3 (Hayakawa et al. Agric. Biol. Chem. 49:2685 (1985)). The naturally occurring compound has the following general structure of Formula I, varying solely in the fatty acid moiety.

Synthetic spicamycin derivatives and their use as anti-tumor agents are described in U.S. Pat. Nos. 5,461,036 and 5,631,238 to Otake et al. The use of spicamycin or derivatives thereof, including KRN5500, to reduce and/or prevent pain is described in U.S. Pat. Nos. 5,905,069, 7,196,071, and 7,375,094 to Borsook et al. KRN5500 has been demonstrated to be effective in rat models of neuropathic pain (Abdi et al., Anesth. Analg. 91:955 (2000); Kobierski et al., Anesth. Analg. 97:174 2003).
The present invention provides improved compositions and methods for treating or preventing pain, e.g., neuropathic pain using spicamycin derivatives.